tacrolimus combined with entecavir on hbv associated glomerulonephritis(hbv-gn)

Conditions: Hepatitis B Virus Associated Nephrotic Syndrome

Summary: this study was to evaluate the efficacy and safety of tacrolimus combined with entecavir antiviral therapy for hbv-associated glomerulonephritis in china. tacrolimus combined with entecavir rapidly and effectively induced remission of hbv-gn in chinese adults. meanwhile, tacrolimus may have a synergistic antiviral effect with entecavir. the study protocol was reviewed and approved by guangdong general hospital's ethic committee, and all participants provided written informed consents. the study will be a prospective, randomized,controlled,single-blind, multi-centre, withdrawal study conducted by guangdong general hospital, guangdong academy of medical sciences.there will be two phases, phase 1, screening and enrolling 112 hbv-gn patients about one year,and phase 2, ongoing follow-up for 24 weeks.the data of all patients will be recorded in the hbv-gn electronic database.before the randomisation, all patients will receive entecavir routine antiviral therapy for two weeks.and then they will be randomized to two different group,the treatment group: tacrolimus combined with entecavir antiviral therapy,the control group: the tacrolimus placebo and entecavir antiviral therapy. the tacrolimus target trough concentration was 5-10 ng/ml during the therapy. the primary outcome variables were the number of patients who reached complete or partial remission (cr or pr) after the 25 week-treatment. cr was deﬁned as \ 50 ml/min/1.73 m2) and pr as proteinuria 0.3-3.0 g/24 h (upcr 300-3000mg/g.cr) and 50% lower than baseline proteinuria plus stable renal function. secondary outcome variables: 1) the number of patients who reached complete or partial remission (cr or pr) after the 13 week-treatment. 2) serum creatinine (scr) increased 2 times the baseline levels or 50% lower than the baseline egfr(according to chronic kidney disease-epi (ckd-epi) )after the 25 week-treatment. 3)serum hbv dna was undetectable(hbv dna\<500copies/ml) at the end of 25 week-treatment. 4) the number of patients who present acute kidney injury at the end of 25 week-treatment.


Eligibility criteria:
inclusion criteria: * male and female patients aged between 18 and 65 years with hbv-gn; * all hbv-gn cases with biopsy-proven; * evidence of chronic hbv infection based on the presence of hbsag, hbeag or hbv dna in the serum;(hbsag, hbeag was positive, hbv dna ≥10\*3 iu/ml). chronic hbv infection lasted for six months, and all patients did not receive the antiviral therapy in the past six months; * proteinuria more than 3.0g/24h, upcr\>3000mg/g.cr, the result will be proofed by at least two tests; * no glucocorticoid and immunosuppressive treatment within the previous 2 weeks. exclusion criteria: * the diagnosis of idiopathic membranous nephropathy(mn), systemic lupus erythematosus, malignancy, diabetes mellitus, severe infections or any other systemic disease known to be associated with secondary mn; * egfr\<30ml/min.1.73m\*2; * renal pathology showed that tubular atrophy or interstitial fibrosis was more than 50%; * the participant is allergy to tacrolimus, entecavir; * history of diabetes mellitus; * history of severe heart disease or cerebrovascular diseases; * other active infection such as cytomegalovirus (cmv),tuberculosis,hepatitis a virus (hav),hepatitis c virus (hcv),hepatitis d virus (hdv); innate or acquired immunodeficiency; liver cirrhosis, liver malignment tumor; * pregnant, trying to become pregnant or breast feeding;

Keywords: hepatitis b virus, tacrolimus,membranous nephropathy